New roles of osteoblasts involved in osteoclast differentiation.
New roles of osteoblasts involved in osteoclast differentiation.
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DOI：
10.5312/wjo.v3.i11.175
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发表时间：
2012-11
影响因子：
1.9
通讯作者：
T. Yamashita;N. Takahashi;N. Udagawa
中科院分区：
文献类型：
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作者：
T. Yamashita;N. Takahashi;N. Udagawa
骨吸收破骨细胞是由单核/巨噬细胞系在成骨细胞的严格控制下形成的。迄今为止，由成骨细胞产生的巨噬细胞集落刺激因子、核因子受体激活剂κB配体和护骨素在破骨细胞分化的调控中起着重要作用。最近的研究表明，成骨细胞通过几种独立于M-CSF、RANKL和OPG产生的机制来调节破骨细胞的形成。体内破骨细胞前体的鉴定表明，成骨细胞参与破骨细胞前体在骨中的分布。白细胞介素34(IL-34)是一种新的c-FMS配体，在维持M-CSF缺陷小鼠脾中破骨细胞前体的储存库中起着关键作用。在破骨细胞形成过程中，IL-34也可以作为成骨细胞产生M-CSF的替代物。WNT5A由成骨细胞产生，通过激活非规范的WNT途径上调RANK的表达来促进破骨细胞的分化。成骨细胞产生的信号素3A通过抑制免疫受体酪氨酸激活基序信号来抑制RANKL诱导的破骨细胞分化。因此，最近的研究结果表明，破骨细胞的分化受到成骨细胞通过几种不同机制的严格调控。这些新发现的分子有望成为骨相关疾病治疗药物的靶点。
Bone-resorbing osteoclasts are formed from a monocyte/macrophage lineage under the strict control of bone-forming osteoblasts. So far, macrophage colony-stimulating factor (M-CSF), receptor activator of nuclear factor-κB ligand (RANKL), and osteoprotegerin (OPG) produced by osteoblasts play major roles in the regulation of osteoclast differentiation. Recent studies have shown that osteoblasts regulate osteoclastogenesis through several mechanisms independent of M-CSF, RANKL, and OPG production. Identification of osteoclast-committed precursors in vivo demonstrated that osteoblasts are involved in the distribution of osteoclast precursors in bone. Interleukin 34 (IL-34), a novel ligand for c-Fms, plays a pivotal role in maintaining the splenic reservoir of osteoclast-committed precursors in M-CSF deficient mice. IL-34 is also able to act as a substitute for osteoblast-producing M-CSF in osteoclastogenesis. Wnt5a, produced by osteoblasts, enhances osteoclast differentiation by upregulating RANK expression through activation of the non-canonical Wnt pathway. Semaphorin 3A produced by osteoblasts inhibits RANKL-induced osteoclast differentiation through the suppression of immunoreceptor tyrosine-based activation motif signals. Thus, recent findings show that osteoclast differentiation is tightly regulated by osteoblasts through several different mechanisms. These newly identified molecules are expected to be promising targets of therapeutic agents in bone-related diseases.